Zovirax tablets 200mg, No. 25

Treatment of infections of the skin and mucous membranes caused by the herpes simplex virus, including primary and recurrent genital herpes;

- prevention of recurrence of infections caused by the herpes simplex virus in patients with normal immune status;

- prevention of infections caused by the herpes simplex virus in immunocompromised patients;

-treatment of chickenpox and herpes zoster;

- treatment of patients with severe immunodeficiency, mainly with HIV infection (CD4 + cell count <200 / mm3, early clinical manifestations of HIV infection and stage of AIDS) and those who underwent bone marrow transplantation.

Inside, during meals, with a full glass of water.

Adults

Treatment of infections caused by the herpes simplex virus: the recommended dose of Zovirax is 200 mg 5 times a day every 4 hours, except for the period of night sleep. Usually, the course of treatment is 5 days, but it can be extended for severe primary infections.

In the case of severe immunodeficiency (for example, after bone marrow transplantation) or in case of impaired absorption from the intestine, the oral dose of Zovirax may be increased to 400 mg 5 times a day. Treatment should be started as early as possible after the onset of the infection; in case of relapses, the drug is recommended to be prescribed already in the prodromal period or when the first elements of the rash appear.

Prevention of recurrence of infections caused by the herpes simplex virus. In patients with normal immune status, the recommended dose of Zovirax is 200 mg 4 times a day (every 6 hours). A more convenient treatment regimen is suitable for many patients - 400 mg 2 times a day (every 12 hours). In some cases, lower doses of Zovirax are effective - 200 mg 3 times a day (every 8 hours) or 2 times a day (every 12 hours). In some patients, interruption of infection can occur with a total daily dose of 800 mg.

Treatment with Zovirax should be interrupted periodically for 6-12 months to identify possible changes in the course of the disease.

Prevention of infections caused by the herpes simplex virus. In immunocompromised patients, the recommended dose of Zovirax is 200 mg 4 times a day (every 6 hours). In the case of severe immunodeficiency (for example, after bone marrow transplantation) or in case of impaired absorption from the intestine, the oral dose of Zovirax may be increased to 400 mg 5 times a day. The duration of the preventive course of therapy is determined by the duration of the period when there is a risk of infection.

Treatment of chickenpox and herpes zoster: the recommended dose of Zovirax is 800 mg 5 times a day; the drug is taken every 4 hours, except for the period of night sleep. The course of treatment is 7 days. The drug should be administered as early as possible after the onset of infection, because in this case, the treatment is more effective.

Treatment of patients with severe immunodeficiency: the recommended dose of Zovirax is 800 mg 4 times a day (every 6 hours). Patients who have undergone bone marrow transplantation, before prescribing Zovirax for oral administration, are usually recommended to undergo a course of IV therapy with Zovirax for 1 month. In clinical trials, the maximum duration of treatment for bone marrow transplant recipients was 6 months (from 1 to 7 months after transplantation). In patients with a detailed clinical picture of HIV infection, the course of treatment with Zovirax was 12 months, but there is reason to believe that longer courses of therapy may be effective in such patients.

For children

Treatment and prevention of herpes simplex virus infections in immunocompromised children:

from 2 years of age and older - the same doses as for adults;

under 2 years old, half the adult dose.

Chickenpox treatment:

over 6 years old - 800 mg 4 times a day;

from 2 to 6 years - 400 mg 4 times a day;

under 2 years old - 200 mg 4 times a day.

More precisely, the dose can be determined at the rate of 20 mg / kg of body weight (but not more than 800 mg) 4 times a day. The course of treatment is 5 days.

There are no data on the prevention of recurrence of herpes simplex virus infections and on the treatment of herpes zoster in children with normal immunity indicators. According to the available very limited information, for the treatment of children over 2 years of age with severe immunodeficiency, the same doses of Zovirax can be used as for the treatment of adults.

Elderly patients. In old age, there is a decrease in the clearance of acyclovir in the body in parallel with a decrease in creatinine clearance.

Elderly patients should receive a sufficient amount of fluid while taking high doses of Zovirax orally; in case of renal failure, they need to decide on reducing the dose of Zovirax.

Patients with renal impairment. In patients with renal insufficiency, oral acyclovir in recommended doses for the treatment and prevention of infections caused by the herpes simplex virus does not lead to the accumulation of the drug to concentrations exceeding the established safe levels. However, in patients with severe renal insufficiency (Cl creatinine <10 ml / min), the dose of Zovirax is recommended to be reduced to 200 mg 2 times a day (every 12 hours).

In the treatment of chickenpox, herpes zoster, as well as in the treatment of patients with severe immunodeficiency, the recommended doses of Zovirax are:

severe renal failure (Cl creatinine <10 ml / min): 800 mg 2 times a day every 12 hours;

moderate renal failure (Cl creatinine 10-25 ml / min) 800 mg 3 times a day every 8 hours.

I / O, adults. In obese patients, dosages are recommended as in adults with normal body weight.

Treatment of infections caused by HSV (with the exception of herpes encephalitis) and VOG - intravenous infusion at a dose of 5 mg / kg every 8 hours.

Treatment of infections caused by VOG and herpetic encephalitis in immunocompromised patients - intravenous infusion at a dose of 10 mg / kg every 8 hours with normal renal function.

Prevention of CMV infection during bone marrow transplantation - intravenous 500 mg / m2 3 times a day with an interval of 8 hours. Duration of treatment is from 5 days before transplantation and up to 30 days after transplantation.

For children

Doses for intravenous infusions in children aged 3 months to 12 years are calculated depending on the surface area of ??the body. In newborns, doses are calculated based on body weight. For HSV infections, a dose of 10 mg / kg every 8 hours is recommended.

Treatment of infections caused by HSV (except herpetic encephalitis) and VOG - intravenous infusion at a dose of 250 mg / m2 every 8 hours.

Treatment of herpetic encephalitis and infections caused by VOG in immunocompromised children - intravenous infusion at a dose of 500 mg / m2 every 8 hours with normal renal function.

Prevention of CMV infection in children over 2 years of age. The paucity of data suggests that children over 2 years of age who have undergone bone marrow transplantation may be given an IV adult dosage of Zovirax. In children with reduced renal function, dose adjustment is required in accordance with the degree of renal failure.

In elderly patients, the clearance of acyclovir in the body decreases in parallel with a decrease in creatinine clearance. Particular attention should be paid to reducing doses of Zovirax in the elderly with reduced creatinine clearance.

In patients with renal insufficiency, IV infusion of Zovirax should be administered with caution. The dose is adjusted depending on the degree of decrease in creatinine clearance:

when Cl creatinine is 25-50 ml / min, the dose is 5-10 mg / kg or 500 mg / m2 every 12 hours;

when Cl creatinine is 10Ц25 ml / min, the dose is 5Ц10 mg / kg or 500 mg / m2 every 24 hours;

with Cl creatinine 0 (anuria) - 10 ml / min: with continuous ambulatory peritoneal dialysis, the dose is 2.5Ц5 mg / kg or 250 mg / m2 every 24 hours; with hemodialysis - 2.5Ц5 mg / kg or 250 mg / m2 every 24 hours and after dialysis.

The course of treatment with Zovirax in the form of intravenous infusion is usually 5 days, but may vary depending on the patient's condition and response to therapy. The duration of treatment for herpes encephalitis and HSV infections in newborns is usually 10 days. The duration of the prophylactic use of Zovirax for intravenous infusion is determined by the duration of the period when there is a risk of infection.

Solution preparation and method of administration

The recommended dose of Zovirax should be administered as a slow intravenous infusion for more than 1 hour.

To prepare a solution of Zovirax with an acyclovir concentration of 25 mg / ml in an ampoule with Zovirax powder, add 10 ml of water for injection or sodium chloride solution for injection (0.9%) and shake gently until the contents of the ampoule are completely dissolved. After dilution, Zovirax's solution can be administered as an intravenous infusion using a special infusion pump that regulates the rate of drug administration.

Another method of infusion is possible, when the prepared Zovirax solution is diluted further to obtain an acyclovir concentration not exceeding 5 mg / ml (0.5%). To do this, add the prepared solution to the selected infusion solution (see below) and shake well to completely mix the solutions. For children and newborns, in whom it is necessary to observe the minimum volumes of infusion, it is recommended to add 4 ml of the prepared solution of Zovirax (100 mg of acyclovir) to 20 ml of the infusion solution.

For adults, it is recommended to use infusion solutions in packages of 100 ml, even if this will give an acyclovir concentration significantly below 0.5%. Thus, one 100 ml infusion solution can be used for any dose of acyclovir between 250 and 500 mg (10 and 20 ml diluted solution). For doses between 500 and 1000 mg of acyclovir, a second infusion solution of this volume should be used.

Zovirax for IV infusion is compatible with the following infusion solutions and remains stable when diluted for 12 hours at room temperature (15 to 25 ? C):

sodium chloride for intravenous infusion (0.45% and 0.9%);

sodium chloride (0.18%) and glucose (4%) for intravenous infusion;

sodium chloride (0.45%) and glucose (2.5%) for intravenous infusion;

Hartmann's solution.

Since no antibacterial preservative is included in the composition of the solutions, dissolution and dilution should be carried out completely under aseptic conditions immediately before the administration of the drug, and the unused solution is destroyed.

If the solution becomes cloudy or crystals fall out, it should be destroyed.

Eye ointment: for adults and children, a strip of ointment 10 mm long is placed in the lower conjunctival sac 5 times a day with an interval of about 4 hours. Treatment must be continued for at least 3 days after recovery.

The tablets are white, round, biconvex, with the inscription 'GXCL3' on one side.

1 tab. acyclovir 200 mg

Excipients: lactose monohydrate, sodium starch glycolate, povidone K30, magnesium stearate, microcrystalline cellulose.

Hypersensitivity to acyclovir or valacyclovir.

• It is prescribed with caution for dehydration and renal failure.

pharmachologic effect

An antiviral drug, a synthetic analogue of a purine nucleoside, which has the ability to inhibit in vitro and in vivo the replication of Herpes simplex viruses type 1 and 2, Varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the most pronounced antiviral activity against Herpes simplex type 1, then, in decreasing order of activity, follow: Herpes simplex type 2, Varicella zoster, EBV and CMV.

The action of acyclovir on viruses is highly selective. Acyclovir is not a substrate for the enzyme thymidine kinase of uninfected cells, therefore it has low toxicity to mammalian cells. Thymidine kinase of cells infected with Herpes simplex viruses type 1 and 2, Varicella zoster, EBV and CMV converts acyclovir into acyclovir monophosphate - a nucleoside analogue, which is then sequentially converted into diphosphate and triphosphate under the action of cellular enzymes. The incorporation of acyclovir triphosphate into the viral DNA strand and the subsequent termination of the strand blocks further viral DNA replication.

In patients with severe immunodeficiency, prolonged or repeated courses of therapy with acyclovir can lead to the formation of resistant strains, and therefore further treatment with acyclovir may be ineffective. Most of the isolated strains with reduced sensitivity to acyclovir showed a relatively low content of viral thymidine kinase, a violation of the structure of viral thymidine kinase or DNA polymerase. The effect of acyclovir on strains of the Herpes simplex virus in vitro can also lead to the formation of strains that are less sensitive to it. No correlation has been established between the sensitivity of Herpes simplex virus strains to acyclovir in vitro and the clinical efficacy of the drug.

Pharmacokinetics

Suction

When taken orally, acyclovir is only partially absorbed from the intestines. When 200 mg acyclovir was taken every 4 hours, the mean plasma CSSmax was 3.1 ?mol (0.7 ?g / ml), and the average CSSmin was 1.8 ?mol (0.4 ?g / ml). When 400 mg and 800 mg of acyclovir were taken every 4 hours, CSSmax was 5.3 ?mol (1.2 ?g / ml) and 8 ?mol (1.8 ?g / ml), respectively, and the average CSSmin was 2.7 ?mol (0.6 ?g / ml) and 4 ?mol (0.9 ?g) / ml), respectively.

Distribution

The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its plasma concentration. Acyclovir to a small extent (9-33%) binds to blood plasma proteins.

Metabolism and excretion

The main metabolite of acyclovir is 9-carboxymethoxy-methylguanine, which accounts for about 10-15% of the administered dose in the urine.

T1 / 2 is 2.5-3.3 hours. Most of the drug is excreted by the kidneys unchanged. The renal clearance of acyclovir significantly exceeds the clearance of creatinine, which indicates the elimination of acyclovir not only by glomerular filtration, but also by tubular secretion. When acyclovir was prescribed 1 hour after taking 1 g of probenecid, T1 / 2 and AUC increased by 18 and 40%, respectively.

Pharmacokinetics in special clinical situations

In patients with chronic renal failure, T1 / 2 of acyclovir averaged 19.5 hours; when carrying out hemodialysis, respectively, 5.7 hours, and the concentration of acyclovir in plasma decreased by approximately 60%.

In the elderly, acyclovir clearance decreases with age in parallel with a decrease in creatinine clearance, but the T1 / 2 of acyclovir changes insignificantly.

With the simultaneous administration of acyclovir and zidovudine to HIV-infected patients, the pharmacokinetic characteristics of both drugs practically did not change.

Side effect

From the digestive system: nausea, vomiting, diarrhea, abdominal pain; rarely - a reversible increase in the level of bilirubin and the activity of hepatic enzymes.

From the hematopoietic system: very rarely - anemia, leukopenia, thrombocytopenia.

From the urinary system: rarely - an increase in the level of urea and creatinine in the blood; very rarely - acute renal failure.

From the side of the central nervous system: headache; rarely - reversible neurological disorders, such as dizziness, confusion, hallucinations, drowsiness, convulsions, coma. Typically, these side effects were observed in patients with renal insufficiency who took the drug in doses higher than the recommended ones.

Allergic reactions: rash, photosensitivity, urticaria, itching; rarely - shortness of breath, angioedema, anaphylaxis.

Others: fatigue; rarely - rapid diffuse hair loss. Since this type of alopecia is observed in various diseases and during therapy with many drugs, its connection with the intake of acyclovir has not been established.

In patients receiving antiretroviral drugs, the additional intake of Zovirax did not cause a significant increase in toxic effects.

Application during pregnancy and lactation

The appointment of Zovirax during pregnancy and lactation (breastfeeding) requires caution and is possible only after assessing the intended benefits to the mother and the potential risk to the fetus and child.

There was no increase in the number of birth defects in children whose mothers received Zovirax during pregnancy compared to the general population.

After taking Zovirax orally at a dose of 200 mg 5 times / day, acyclovir was determined in breast milk at concentrations of 0.6-4.1% of plasma concentrations. At such concentrations in breast milk, children who are breastfed can receive acyclovir at a dose of up to 300 mcg / kg / day.

Application for impaired renal function

In patients with renal insufficiency, oral acyclovir in recommended doses for the treatment and prevention of infections caused by Herpes simplex viruses does not lead to the accumulation of the drug to concentrations exceeding the established safe levels. However, in patients with CC less than 10 ml / min, the dose of Zovirax is recommended to be reduced to 200 mg 2 times / day (every 12 hours). For the treatment of chickenpox, herpes zoster, as well as for the treatment of patients with severe immunodeficiency with CC less than 10 ml / min, the recommended doses of Zovirax are 800 mg 2 times / day every 12 hours; with CC 10-25 ml / min 800 mg 3 times / day every 8 hours.

Application in children

Treatment and prevention of infections caused by Herpes simplex viruses in immunocompromised children aged 2 years and older - the same doses as for adults; under 2 years of age, half the adult dose.

For the treatment of chickenpox in children over 6 years of age, the drug is prescribed in a single dose of 800 mg; from 2 to 6 years - 400 mg; under 2 years old - 200 mg. The frequency of admission is 4 times / day. More precisely, a single dose can be determined at the rate of 20 mg / kg of body weight (but not more than 800 mg). The course of treatment is 5 days.

There are no data on the use of Zovirax for the prevention of recurrence of infections caused by Herpes simplex viruses and for the treatment of herpes zoster in children with normal immunity indicators.

According to the available very limited information, for the treatment of children over 2 years of age with severe immunodeficiency, the same doses of Zovirax can be used as for the treatment of adults.

Use in elderly patients

Elderly patients should receive a sufficient amount of fluid while taking Zovirax inside in high doses.

special instructions

ѕациенты, принимающие внутрь «овиракс в высоких дозах, должны получать достаточное количество жидкости.

ѕередозировка

ѕри случайном однократном приеме ацикловира внутрь в дозах до 20 г токсические эффекты не зарегистрированы.

—имптомы: нарушени¤ со стороны ? “ (тошнота, рвота) и неврологические нарушени¤ (головна¤ боль и спутанность сознани¤); иногда - одышка, диаре¤, нарушение функции почек, летарги¤, судороги, кома.

Ћечение: тщательное медицинское наблюдение с целью вы¤влени¤ возможных симптомов интоксикации. ¬озможно применение гемодиализа.

Ћекарственное взаимодействие

 линически значимых взаимодействий «овиракса с другими лекарственными препаратами не отмечалось.

Ѕлокаторы кальциевых каналов и циметидин увеличивают AUC ацикловира и снижают его почечный клиренс (коррекции режима дозировани¤ «овиракса не требуетс¤).

With the simultaneous use of Zovirax with drugs excreted by active tubular secretion, it is possible to increase the concentration of active substances or their metabolites in plasma (caution is needed when prescribing such combinations).

The combined use of acyclovir and mycophenolate mophenil, an immunosuppressant used in organ transplantation, leads to an increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mophenyl.